Abstract
The purpose of this study is to assess the changes in the expression of angiogenesis-related genes in the cellular component of the blood from preeclamptic patients. Blood samples were obtained from the preeclampsia (PE) and control participants. Cellular RNA was analyzed by reverse transcription polymerase chain reaction (PCR) to identify any angiogenesis-related genes and thereby assess the mRNA expression among women with PE and controls during weeks 35 to 41 of gestation. Significant differences were observed between PE and controls in all of the angiogenesis-related genes examined. In PE, for the increased expression of transforming growth factor-β1 (TGF-β1), endoglin and fms-like tyrosine kinase-1 (Flt-1); and the reduced expression of vascular endothelial growth factor (VEGF), placental growth factor (PlGF). fms-Like tyrosine kinase-1 and endoglin significantly correlated with the systolic pressure, while VEGF, Flt-1, and endoglin all correlated with proteinuria. An altered expression of angiogenesis-related genes was demonstrated in the cellular component of blood from preeclamptic patients. These findings indicate that this approach may offer an alternative way for evaluating the patho-genesis of PE.
Article PDF
Similar content being viewed by others
References
Redman CW, Sargent IL. Latest advances in understanding preeclampsia. Science. 2005;308(5728):1592–1594.
Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet. 2005;365(9461):785–799.
Levine RJ, Lam C, Qian C, et al. Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. N Engl J Med. 2006;355(10):992–1005.
Levine RJ, Maynard SE, Qian C, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004;350(7):672–683.
Venkatesha S, Toporsian M, Lam C, et al. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med. 2006;12(6):642–649.
Gerber HP, Hillan KJ, Ryan AM, et al. VEGF is required for growth and survival in neonatal mice. Development. 1999;126(6):1149–1159.
Clark DE, Smith SK, Sharkey AM, Charnock-Jones DS. Localization of VEGF and expression of its receptors flt and KDR in human placenta throughout pregnancy. Hum Reprod. 1996;11(5):1090–1098.
Ferrara N. Role of vascular endothelial growth factor in regulation of physiological angiogenesis. Am J Physiol Cell Physiol. 2001;280(6):C1358–C1366.
He H, Venema VJ, Gu X, Venema RC, Marrero MB, Caldwell RB. Vascular endothelial growth factor signals endothelial cell production of nitric oxide and prostacyclin through flk-1/KDR activation of c-Src. J Biol Chem. 1999;274(35):25130–25135.
He Y, Smith SK, Day KA, Clark DE, Licence DR, Charnock-Jones DS. Alternative splicing of vascular endothelial growth factor (VEGF)-R1 (FLT-1) pre-mRNA is important for the regulation of VEGF activity. Mol Endocrinol. 1999;13(4):537–545.
Yang JC, Haworth L, Sherry RM, et al. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med. 2003;349(5):427–434.
Maynard SE, Min JY, Merchan J, et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest. 2003;111(5):649–658.
Gougos A, St Jacques S, Greaves A, et al. Identification of distinct epitopes of endoglin, an RGD-containing glycoprotein of endothelial cells, leukemic cells, and syncytiotrophoblasts. Int Immunol. 1992;4(1):83–92.
St-Jacques S, Forte M, Lye SJ, Letarte M. Localization of endoglin, a transforming growth factor-beta binding protein, and of CD44 and integrins in placenta during the first trimester of pregnancy. Biol Reprod. 1994;51(3):405–413.
Sanchez-Elsner T, Botella LM, Velasco B, Langa C, Bernabeu C. Endoglin expression is regulated by transcriptional cooperation between the hypoxia and transforming growth factor-beta pathways. J Biol Chem. 2002;277(46):43799–43808.
Bourdeau A, Dumont DJ, Letarte M. A murine model of her-editary hemorrhagic telangiectasia. J Clin Invest. 1999; 104(10):1343–1351.
Toporsian M, Gros R, Kabir MG, et al. A role for endoglin in coupling eNOS activity and regulating vascular tone revealed in hereditary hemorrhagic telangiectasia. Circ Res. 2005;96(6):684–692.
Purwosunu Y, Sekizawa A, Farina A, et al. Evaluation of physiological alterations of the placenta through analysis of cell-free mRNA concentrations of angiogenic factors. Am J Obstet Gynecol. 2007 IN PRESS.
Purwosunu Y, Sekizawa A, Koide K, et al. Cell-free mRNA concentrations of plasminogen activator inhibitor-1 and tissue-type plasminogen activator are increased in the plasma of pregnant women with preeclampsia. Clin Chem. 2007;53(3):399–404.
Purwosunu Y, Sekizawa A, Farina A, et al. Cell-free mRNA concentrations of CRH, PLAC1, and selectin-P are increased in the plasma of pregnant women with preeclampsia. Prenat Diagn. 2007;27(8):772–777.
Okazaki S, Sekizawa A, Purwosunu Y, Iwasaki M, Farina A, Okai T. Measurement of mRNA of trophoblast-specific genes in cellular and plasma components of maternal blood. J Med Genet. 2006;43(9):e47.
Okazaki S, Sekizawa A, Purwosunu Y, Farina A, Wibowo N, Okai T. Placenta-derived, cellular messenger RNA expression in the maternal blood of preeclamptic women. Obstet Gynecol. 2007;110(5):1130–1136.
ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet. 2002;77(1):67–75.
Farina A, Sekizawa A, Purwosunu Y, et al. Quantitative distribution of a panel of circulating mRNA in pree-clampsia versus controls. Prenat Diagn. 2006;26(12): 1115–1120.
Obiekwe BC, Sturdee D, Cockrill BL, Chard T. Human pla-cental lactogen in pre-eclampsia. Br J Obstet Gynaecol. 1984;91(11):1077–1080.
Shore VH, Wang TH, Wang CL, Torry RJ, Caudle MR, Torry DS. Vascular endothelial growth factor, placenta growth factor and their receptors in isolated human tropho-blast. Placenta. 1997;18(8):657–665.
Taylor RN, Grimwood J, Taylor RS, McMaster MT, Fisher SJ, North RA. Longitudinal serum concentrations of placental growth factor: evidence for abnormal placental angiogenesis in pathologic pregnancies. Am J Obstet Gynecol. 2003; 188(1):177–182.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Purwosunu, Y., Sekizawa, A., Yoshimura, S. et al. Expression of Angiogenesis-Related Genes in the Cellular Component of the Blood of Preeclamptic Women. Reprod. Sci. 16, 857–864 (2009). https://doi.org/10.1177/1933719109336622
Published:
Issue Date:
DOI: https://doi.org/10.1177/1933719109336622